OP0239 DOES EARLY IMMUNOSUPPRESSIVE THERAPY PREVENT SYSTEMIC SCLEROSIS ASSOCIATED INTERSTITIAL LUNG DISEASE?
Authors: A. Velauthapillai, M. Bootsma, C. Bruni, O. Distler, C. Van den Ende, M. Vonk
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic sclerosis (SSc) is an auto-immune disease characterized by a triad of inflammation, vascular damage and fibrosis. Interstitial lung disease(ILD) is a major contributor to impaired quality of life and a leading cause of death in these patients. While recent studies reported a favorable effect on disease course when starting immunosuppressive(IMS) therapy in mild and moderate ILD, no definite evidence of a preventive mechanism of IMS therapy for ILD onset is established(1, 2). <h3>Objectives</h3> The objective of our study was to explore the association between timing of start IMS therapy and the development of ILD. <h3>Methods</h3> A combined cohort was created from the EUSTAR database and Nijmegen Systemic Sclerosis cohort, including patients: 1) aged 18 years or older 2) treated with IMS (i.e. mycophenolate mofetil, methotrexate, cyclophosphamide and rituximab) after SSc diagnosis 3) negative for signs of ILD on high-resolution CT(HRCT) at or within 2 months after start treatment and 4) no prior treatment with biological or antifibrotic in the preceding years. Data between start of first IMS treatment and five years follow-up were analysed. Disease duration (time between first non-Raynaud phenomenon and start IMS) was dichotomized into early and late treatment using a cut-off point of 3 years. ILD-free survival (absence of HRCT confirmed ILD diagnosis) was assessed with unadjusted Kaplan Meier analysis on complete cases and a cox proportional hazard analysis on imputed data adjusting for confounders. <h3>Results</h3> We identified 1037 patients meeting the eligibility criteria. The early treatment group (n= 539, 52 %) showed a higher prevalence of male sex, diffuse cutaneous SSc (dcSSc, 52.9% vs 36.4%, p= 0.001), anti-topoisomerase I antibody positivity (ATA, 51.0% vs. 42.5%, p= 0.01), anti-RNA polymerase III antibody positivity (ARA, 11.7% vs. 5.4%, p=0.009) and elevated C-reactive protein levels (30.6% vs. 22.6%, p=0.03). Further, patients in the early group had a higher modified Rodnan skin score (mRSS, mean(SD) 13.3(9.7) vs. 9.7(8.9), p= 0.001). The incidence of ILD was 46.1% after mean(SD) 3.6(1.4) years of treatment and not significantly different between the groups (mean(95% CI); early: 47% (43-51) vs. late: 45%(40-50), p= 0.64). The unadjusted Kaplan-Meier survival curve on complete cases (Figure 1) shows no differences in ILD-free survival rates between the early and late treatment group. The hazard ratio for ILD in the early treatment group was 1.11 (95% CI: 0.91-1.36) adjusting for gender, dcSSc, Caucasian ethnicity, ATA, ARA, age, forced vital capacity and diffusing capacity for carbon monoxide at baseline. <h3>Conclusion</h3> Our finding did not confirm a preventive role of early vs. late timing of IMS therapy on ILD development. However, our findings should be interpreted with caution, considering the high inflammatory, ATA-positive enriched nature of the cohort selected, as well as confounding by indication, which cannot be ruled out also after adjusting for other confounding factors. <h3>References</h3> [1]Hoa S et al., Rheumatology (Oxford). 2020;59(5):1108-17. [2]Hoa S et al., Chest. 2021;160(6):2158-62. <h3>Disclosure of Interests</h3> Arthiha Velauthapillai: None declared, Merle Bootsma: None declared, Cosimo Bruni Speakers bureau: Eli Lilly, Consultant of: Eli Lilly, Grant/research support from: Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC). Educational grants from AbbVie., Oliver Distler Speakers bureau: 4P-Pharma, Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur., Consultant of: 4P-Pharma, Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Redxpharma, Roivant, Sanofi and Topadur., Grant/research support from: 4P-Pharma, Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer Ingelheim, Corbus, CSL Behring, 4P Science, Galapagos, Glenmark, Horizon, Inventiva, Janssen, Kymera, Lupin, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, MSD, Novartis, Prometheus, Redxpharma, Roivant, Sanofi, Topadur, Kymera and Mitsubishi Tanabe., Cornelia van den Ende: None declared, Madelon Vonk Speakers bureau: Boehringer Ingelheim, Bristol-Myers Squibb, GSK, Janssen, MSD, Novartis and Roche, Consultant of: Boehringer Ingelheim and Janssen, Grant/research support from: Research grants from Boehringer Ingelheim, Janssen,Ferrer and Galapagos.